1. Field of the Invention
The invention relates to a method for fabricating a biosensor chip, and more particularly to a method for fabricating a biosensor chip utilizing nano-technology. The invention also relates to a biosensor chip made by the method.
2. Description of the Related Art
There are various chemo-sensors, for example, a taste sensor, a smell sensor, a hormone receptor of an endocrine system, a chemical transmitter substance and a receptor protein of a neutron-transmitting system, an antibody or an antigen of an immune system, or the like, in an organism so as to form an assembly of chemo-receptors in the organism. The existence of a specific substance or molecule and the specific physiological reaction produced thereby may be detected using a specific selection and sensitivity of a specific one of the chemo-receptors to the specific substance or molecule.
A biosensor chip is developed utilizing the aforesaid principle. A receptor molecule or substance mounted on a specific material or device forms a specific bonding to a substance to be detected, a physical or chemical measurement is conducted, and a concentration of the substance to be detected is determined according to the measurement. The biosensor chip is primarily composed of a receptor which has a specific bonding capability for a substance to be detected, and a substrate which will produce variation in charge, thickness, mass, optical properties, or the like when the receptor bonds to the substance to be detected. Therefore, the biosensor chip can be used for detecting a specific substance and the concentration thereof by using a specific receptor which has a specific bonding capability for the specific substance to be detected and a variation of a specific physical property.
A conventional biosensor chip is produced on a silicon substrate using a semiconductor process. The process is relatively complicated and costly. Detection error will increase after repeated use as a result of damage during a cleaning procedure. The structure of the conventional biosensor chip is liable to be affected when detection is conducted in a solution, which may result in signal interference and unstable detection result. Therefore, the conventional biosensor chip is disadvantageous in terms of detection stability and durability.
Because nano-materials have specific characteristics in size and physical properties, they have been applied to the biosensor chip so as to improve structural stability and sensitivity of the biosensor chip and to provide the biosensor chip with better durability and detection sensitivity and precision.
Nano-material usually includes nanoparticles, nanofiber, nano-film, and nano-bulk. Among others, since nanoparticles have been developed for a longer period of time, technologies thereof are more mature than others. Further, as nanofiber and nano-film are made from nanoparticles, production of nanoparticles is relatively important. In general, methods of producing nanoparticles may be classified into physical method and chemical method.
A major example of the chemical method is chemical reduction. In the chemical reduction, nanoparticles are formed through reduction of metal ions in a solution, to which a protecting agent is added so as to maintain uniform distribution of the nanoparticles in the solution and prevent aggregation of the nanoparticles. After the nanoparticles are covered by the protecting agent, a substrate, which has a surface disposed with an organic functional group, is provided for formation of a self-assembly nanostructure, such as nanoparticles, thereon through static attraction force and chemical bonding therebetween. Solutions containing organic materials, such as toluene and thiol-containing organic molecules, are usually used in the chemical reduction. However, the organic materials are likely to contaminate the environment and are harmful to human health.
Examples of physical methods for producing nanoparticles include high temperature annealing, electron beam irradiation, heavy ion irradiation, pulsed laser irradiation, and nanolithography. In the first four of the aforesaid physical methods, a thin film is heated so as to form cracks, become discontinuous, and be melted. Thereafter, spherical nanoparticles are formed by surface tension forces. In the last one of the aforesaid physical methods, a substrate is covered by a specific mask. For example, nano-scale silicon particles are arranged in a hexagonal closed-packed structure. Subsequently, a metal is deposited on interstices of the hexagonal closed-packed structure such that the nanoparticles are formed and arranged in a triangular array. However, the above-mentioned five physical methods have the following disadvantages.
In the high temperature annealing method, raising and lowering of temperature require a long period of time, which results in time-consumption and lower efficiency, and non-uniform morphology and easy aggregation of the nanoparticles.
In the electron beam irradiation method, expensive equipment, such as an electron gun, is needed. In addition, since an electron beam generated from the electron gun can merely focus on a limited region on the substrate in each operation, a long time is required for producing nanoparticles on the substrate having a large area. Thus, the method is also less effective.
In the heavy ion irradiation method, the disadvantages are similar to those in the electron beam irradiation method, and the application thereof is still limited to academic study.
The pulsed laser irradiation method is also less effective because a laser source can irradiate only a small region of the substrate and needs to move back and forth to treat a large area of the substrate.
In the nanolithography method, although mass production of nanoparticles is possible, the method is complicated and time-consuming, and requires organic solvents to clean the substrate, which is not environmentally friendly.
The structure and the production efficiency of the substrate for the conventional biosensor chip may be improved by cooperating with a novel method for producing nanoparticles. In addition to reducing the production cost, the amount of the target material may be detected by utilizing the characteristics of the nanoparticles to provide physical variation required for the biosensor chip, thereby producing an effect better than that of the conventional biosensor chip.
There are researches directed to disposal of receptors on surfaces of metallic nanoparticles to detect a target material via variation of spectrum signal of the metallic nanoparticles. However, when the receptors disposed on the surfaces of the metallic nanoparticles have relatively large thickness, for example, when it is required to dispose multiple layers of molecules for forming the receptors on the surfaces of the metallic nanoparticles, the target material to be detected is then relatively far from the metallic nanoparticles, which results in the disadvantage in which variation of the spectrum signal of the metallic nanoparticles is less sensitive for detecting whether the target material has bonded to the receptors or not.